A nonfibrous shell (red boundary) and other misfolded proteins (blue) accumulate around an amyloid array (yellow) in yeast lacking the Hsp70 protein Ssa1.

A nonfibrous shell (red boundary) and other misfolded proteins (blue) accumulate around an amyloid array (yellow) in yeast lacking the Hsp70 protein Ssa1.

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O’Driscoll et al. reveal how Hsp70 chaperones and their cofactors affect the deposition of amyloid aggregates in yeast.

Prions are misfolded proteins that convert other prion proteins to the misfolded, amyloid state, causing them to aggregate into fibrils. Yeast cells sequester prion fibrils into compact aggregates, a process assisted by the chaperone Hsp70 and its cochaperone Hsp40. In cooperation with Hsp70, the protein remodeling factors Hsp110 and Hsp104 fragment amyloid fibrils and promote prion formation and propagation.

O’Driscoll et al. investigated how the Hsp70 system interacts with amyloid aggregates using a fluorescently tagged version of the yeast prion [PSI+] that, when overexpressed, forms a highly ordered cytoplasmic array of amyloid fibrils. Correlative fluorescence and electron tomography showed that, whereas Hsp70 and Hsp40 are present throughout these aggregates, Hsp104 is present around their outer surface, and Hsp110 is not concentrated there. However, when individual Hsp70 isoforms were deleted, Hsp110 was also recruited to the surface layer, and electron microscopy revealed that this layer contained a nonfibrous form of the prion.

The authors speculate that the actions of Hsp104 and Hsp110 result in formation of the nonfibrillar shell by dissolving existing amyloid fibrils from the outside in. Consistent with this, overexpression of either Hsp104 or Hsp110 disrupted fibril structure and packing. On the other hand, Hsp110-deficient cells had longer amyloid fibrils, suggesting that Hsp110 regulates fibril length. Senior author Helen Saibil is interested to see whether, and how, these interactions might occur in other types of amyloid aggregates.

O’Driscoll
,
J.
, et al
.
2015
.
J. Cell Biol.

Author notes

Text by Caitlin Sedwick